title: Endogenously generated 2-arachidonoylglycerol plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow in rats.
abstract: We previously reported the involvement of brain diacylglycerol lipase and cyclooxygenase in intracerebroventricularly (i.c.v.) administered bombesin-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats. Diacylglycerol can be hydrolyzed by diacylglycerol lipase into 2-arachidonoylglycerol, which may be further hydrolyzed by monoacylglycerol lipase into arachidonic acid, a substrate of cyclooxygenase. 2-Arachidonoylglycerol is a major endocannabinoid, which can inhibit synaptic transmission by presynaptic cannabinoid CB(1) receptors. Released 2-arachidonoylglycerol is rapidly inactivated by uptake into cells and enzymatic hydrolysis. In the present study, we examined the involvement of brain 2-arachidonoylglycerol and its regulatory role in the bombesin-induced central activation of adrenomedullary outflow using anesthetized rats. The elevation of plasma noradrenaline and adrenaline induced by a sub-maximal dose of bombesin (1 nmol/animal, i.c.v.) was reduced by MAFP (monoacylglycerol lipase inhibitor) (0.28 and 0.7 μmol/animal, i.c.v.), JZL184 (selective monoacylglycerol lipase inhibitor) (0.7 and 1.4 μmol/animal, i.c.v.), ACEA (CB(1) receptor agonist) (0.7 and 1.4 μmol/animal, i.c.v.) and AM 404 (endocannabinoid uptake-inhibitor) (80 and 250 nmol/animal, i.c.v.), while AM 251 (CB(1) receptor antagonist) (90 and 180 nmol/animal, i.c.v.) potentiated the response induced by a small dose of bombesin (0.1 nmol/animal, i.c.v.). These results suggest a possibility that 2-arachidonoylglycerol is endogenously generated in the brain during bombesin-induced activation of central adrenomedullary outflow, thereby inhibiting the peptide-induced response by activation of brain CB(1) receptors in rats.
authors.affiliation: Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan. shimizu@kochi-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Lianyi
authors.initials: L
authors.lastname: Lu
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005989:Glycerides / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists
chemical_list: D001095:Arachidonic Acids; D052117:Benzodioxoles; D063385:Cannabinoid Receptor Modulators; D002395:Catecholamines; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; C534333:JZL 184; D010880:Piperidines; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D001839:Bombesin; C107594:N-(4-hydroxyphenyl)arachidonylamide